The neural RNA-binding protein Musashi1 translationally regulates mammalian numb gene expression by interacting with its mRNA

Mol Cell Biol. 2001 Jun;21(12):3888-900. doi: 10.1128/MCB.21.12.3888-3900.2001.


Musashi1 (Msi1) is an RNA-binding protein that is highly expressed in neural progenitor cells, including neural stem cells. In this study, the RNA-binding sequences for Msi1 were determined by in vitro selection using a pool of degenerate 50-mer sequences. All of the selected RNA species contained repeats of (G/A)U(n)AGU (n = 1 to 3) sequences which were essential for Msi1 binding. These consensus elements were identified in some neural mRNAs. One of these, mammalian numb (m-numb), which encodes a membrane-associated antagonist of Notch signaling, is a likely target of Msi1. Msi1 protein binds in vitro-transcribed m-numb RNA in its 3'-untranslated region (UTR) and binds endogenous m-numb mRNA in vivo, as shown by affinity precipitation followed by reverse transcription-PCR. Furthermore, adenovirus-induced Msi1 expression resulted in the down-regulation of endogenous m-Numb protein expression. Reporter assays using a chimeric mRNA that combined luciferase and the 3'-UTR of m-numb demonstrated that Msi1 decreased the reporter activity without altering the reporter mRNA level. Thus, our results suggested that Msi1 could regulate the expression of its target gene at the translational level. Furthermore, we found that Notch signaling activity was increased by Msi1 expression in connection with the posttranscriptional down-regulation of the m-numb gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Base Sequence
  • DNA Primers / genetics
  • Down-Regulation
  • Fungal Proteins / genetics
  • Genes, Reporter
  • In Vitro Techniques
  • Ligands
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice
  • Models, Biological
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism*
  • Neurons / cytology
  • Neurons / metabolism
  • Nucleic Acid Conformation
  • Protein Binding
  • Protein Biosynthesis
  • RNA / chemistry
  • RNA / genetics
  • RNA / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism*
  • Receptors, Notch
  • Saccharomyces cerevisiae Proteins*
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Transcriptional Activation


  • DNA Primers
  • Fungal Proteins
  • HES1 protein, S cerevisiae
  • Ligands
  • Membrane Proteins
  • Msi1h protein, mouse
  • Nerve Tissue Proteins
  • Numb protein, mouse
  • RNA, Messenger
  • RNA-Binding Proteins
  • Receptors, Notch
  • Saccharomyces cerevisiae Proteins
  • RNA